The RNA export factor, Nxt1, is required for tissue specific transcriptional regulation.
The RNA export factor, Nxt1, is required for tissue specific transcriptional regulation.
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DOI：
10.1371/journal.pgen.1003526
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发表时间：
2013-06
期刊：
影响因子：
4.5
通讯作者：
White-Cooper H
中科院分区：
文献类型：
--
作者：
Caporilli S;Yu Y;Jiang J;White-Cooper H
高度保守的Nxf/NxT(TAP/p15)RNA核输出途径通过与mRNAs相互作用并促进它们通过核孔，对大多数mRNAs从细胞核输出是重要的。Nxt1对于生存是必不可少的；利用部分功能等位基因的丧失，我们揭示了该基因在组织特异性转录中的作用。我们发现许多果蝇睾丸特异的mRNAs需要Nxt1来积累。需要Nxt1的转录本也依赖于睾丸特异的转录复合体TMAC。我们发现Nxt1的缺失导致TMAC靶标转录减少。来自TMAC依赖启动子的报告转录本在Nxt1突变体中表达不足，但如果由TMAC非依赖启动子驱动，相同的转录本在突变体中积累。因此，在果蝇初级精母细胞中，用于激活转录本表达的转录因子，而不是RNA序列本身或核心转录机制，决定了这种表达是否需要Nxt1。此外，我们还发现，无内含子基因的转录本比含内含子基因的转录本对Nxt1功能的丧失更敏感，并提出了一种转录本处理反馈以提高组织特异性转录复合体活性的机制。在多细胞生物中，分化的细胞具有特定细胞类型的基因表达谱。精子的产生是特别特殊的，因此，超过5%的基因仅在精子前体细胞中表达，称为初级精母细胞。这些基因的表达依赖于一种仅在精母细胞中活跃的特定转录调节复合体(TMAC)。在这篇文章中，我们证明了一个因子，Nxt1，其先前的特征功能是将RNA从细胞核运输到细胞质，也是许多睾丸特异转录本表达所必需的。缺乏Nxt1的精母细胞不能表达许多依赖于TMAC的基因，我们证明这种影响的部分原因是转录减少。我们进一步证明，通过剪接对RNA的处理可以部分抵消TMAC依赖基因表达中对Nxt1的需求。我们的数据揭示了核心RNA处理途径和组织特异性转录因子之间意想不到的联系。
The highly conserved, Nxf/Nxt (TAP/p15) RNA nuclear export pathway is important for export of most mRNAs from the nucleus, by interacting with mRNAs and promoting their passage through nuclear pores. Nxt1 is essential for viability; using a partial loss of function allele, we reveal a role for this gene in tissue specific transcription. We show that many Drosophila melanogaster testis-specific mRNAs require Nxt1 for their accumulation. The transcripts that require Nxt1 also depend on a testis-specific transcription complex, tMAC. We show that loss of Nxt1 leads to reduced transcription of tMAC targets. A reporter transcript from a tMAC-dependent promoter is under-expressed in Nxt1 mutants, however the same transcript accumulates in mutants if driven by a tMAC-independent promoter. Thus, in Drosophila primary spermatocytes, the transcription factor used to activate expression of a transcript, rather than the RNA sequence itself or the core transcription machinery, determines whether this expression requires Nxt1. We additionally find that transcripts from intron-less genes are more sensitive to loss of Nxt1 function than those from intron-containing genes and propose a mechanism in which transcript processing feeds back to increase activity of a tissue specific transcription complex. In multicellular organisms, differentiated cells have a cell-type specific profile of gene expression. Sperm production is particularly specialised, and as a result over 5% of all genes are expressed exclusively in the sperm precursor cells, termed primary spermatocytes. Expression of these genes depends on a particular transcription regulation complex (tMAC) only active in spermatocytes. In this paper we show that a factor, Nxt1, whose previously characterised function is in transport of RNA from the cell nucleus to the cytoplasm, is also required for expression of many testis-specific transcripts. Spermatocytes deficient for Nxt1 fail to express many tMAC-dependent genes, and we show that this effect is due in part to reduced transcription. We further show that processing of the RNA, via splicing, can partially offset the need for Nxt1 in expression of tMAC-dependent genes. Our data reveal an unexpected link between the core RNA processing pathway and a tissue-specific transcription factor.
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